Τίτλος:
Hepatic senescence accompanies the development of NAFLD in non-aged mice independently of obesity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Senescence is considered to be a cardinal player in several chronic inflammatory and metabolic pathologies. The two dominant mechanisms of senescence include replicative senescence, predominantly depending on age-induced telomere shortening, and stress-induced senescence, triggered by external or intracellular harmful stimuli. Recent data indicate that hepatocyte senes-cence is involved in the development of nonalcoholic fatty liver disease (NAFLD). However, previ-ous studies have mainly focused on age-related senescence during NAFLD, in the presence or ab-sence of obesity, while information about whether the phenomenon is characterized by replicative or stress-induced senescence, especially in non-aged organisms, is scarce. Herein, we subjected young mice to two different diet-induced NAFLD models which differed in the presence of obesity. In both models, liver fat accumulation and increased hepatic mRNA expression of steatosis-related genes were accompanied by hepatic senescence, indicated by the increased expression of senes-cence-associated genes and the presence of a robust hybrid histo-/immunochemical senescence-spe-cific staining in the liver. Surprisingly, telomere length and global DNA methylation did not differ between the steatotic and the control livers, while malondialdehyde, a marker of oxidative stress, was upregulated in the mouse NAFLD livers. These findings suggest that senescence accompanies NAFLD emergence, even in non-aged organisms, and highlight the role of stress-induced senes-cence during steatosis development independently of obesity. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Moustakas, I.I.
Katsarou, A.
Legaki, A.-I.
Pyrina, I.
Ntostoglou, K.
Papatheodoridi, A.-M.
Gercken, B.
Pateras, I.S.
Gorgoulis, V.G.
Koutsilieris, M.
Chavakis, T.
Chatzigeorgiou, A.
Περιοδικό:
International Journal of Molecular Sciences
Λέξεις-κλειδιά:
malonaldehyde; messenger RNA; messenger RNA, adult; animal experiment; animal model; Article; cell aging; controlled study; disease course; DNA methylation; female; gene expression; immunohistochemistry; liver cell; liver fatty degeneration; male; mouse; nonalcoholic fatty liver; nonhuman; obesity; oxidative stress; steatosis; telomere length; upregulation; young adult; animal; C57BL mouse; insulin resistance; lipid diet; lipid peroxidation; liver; liver cell; metabolism; nonalcoholic fatty liver; obesity; pathology; telomere; ultrastructure, Animals; Cellular Senescence; Diet, High-Fat; DNA Methylation; Female; Hepatocytes; Insulin Resistance; Lipid Peroxidation; Liver; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress; RNA, Messenger; Telomere
DOI:
10.3390/ijms22073446
